Symposium:
Current Concepts of Calcium Absorption
Current Concepts of Calcium Absorption: An Overview Department of BioStructure and Function, University of Connecticut Health Center, Farmington, CT 06030 Transepithelial calcium transport in the intestine proceeds by two routes: a transcellular and a paracellular pathway (1). The transcellular route is dominant in the proximal intestine, largely the duodenum, whereas paracellular calcium movement takes place throughout the length of the intestine (2). Transcel lular movement involves three steps: I) entry across the brush border membrane of the enterocyte, 2) intracellular movement and 3) extrusion across the basolateral membrane. Directionality of the movement is assured by the cell structure, the brush border being located at the luminal cell surface, from which calcium enters the cell, whereas extrusion occurs at the basolateral membrane, i.e., the serosal pole of the cell. Moreover, because the extrusion capacity of the CaATPase, the pump enzyme, exceeds the rates of entry and intracellular diffusion, directionality is also as sured functionally. Entry into the cell is down an electrochemical gra dient and in all likelihood uses calcium channels (3). However, the existence of calcium channels in the brush border membrane of mucosal cells still awaits experimental proof. Calcium entry into the cell, as evaluated by uptake measurements that use right sideout brush border membrane vesicles, has been de scribed as the sum of a saturable and a nonsaturable step (4-7). The saturable step may represent the es tablished and significant binding of calcium to the in ner aspect of the brush border membrane vesicle (5, 8). It may also represent a carrier-mediated transport step (6, 9). However, if that were the case it would mean the enterocyte is equipped with two pump-leak systems, working in opposite directions. This is pos sible, but seems unlikely. Inside the cell, calcium must move through the cy toplasm. The rate of self-diffusion of calcium in an enterocyte such as the ileal cell has been calculated to be nearly two orders of magnitude too slow to allow calcium transfer to occur at the experimentally verified rate of transcellular movement (1). A cytosolic cal cium-binding protein, calbindin-9K, discovered some 25 years ago by Wasserman and colleagues (10), occurs
in duodenal cells at high enough concentrations (1) to assure a rate of intracellular flux sufficient to satisfy the established transcellular transport rate. Lysosomes and perhaps other mobile organelles may contribute to intracellular calcium movement (11). However, the quantitative considerations that have led to the pro posal that calbindin ferries calcium intracellularly (1, 12-15) must apply to all intracellular movement of calcium. Calcium extrusion is effected by the Ca-ATPase (16), with the Na+/Ca2+ exchanger probably contrib uting little to calcium transport (17). The capacity of this type of pump is some 25-30 nmol Ca-mg pro tein"1-min"1 (3). It should be emphasized, however, that the Ca-ATPase of the enterocyte has not yet been isolated or cloned. Hence, we do not know whether the cDNA coding a plasma membrane pump that has been isolated from a human teratoma library (18) is the same as that specifying the Ca-ATPase of the in testinal cell, nor whether the two Ca-ATPases are identical. Inasmuch as some Ca-ATPases are inhibited by vanadate, whereas this is not true for the kidney Ca-ATPase (19), and because the optimum pH of the liver Ca-ATPase differs from that of the plasma mem brane enzyme (20), all calcium pump molecules do not appear to be identical. Extrusion is against an electrochemical gradient. However, the overall transport, i.e., from intestinal lumen to the fluid bathing the serosal pole of the in testinal cell, is usually downhill, at least from a con centration viewpoint, inasmuch as the luminal calcium concentration is usually higher than the body fluid concentration of ~ 1 mmol Ca2+/L. 1Presented as part of a symposium: Current Concepts of Calcium Absorption, given at the 75th Annual Meeting of the Federation of American Societies for Experimental Biology, Atlanta, GA, April 22, 1991. The symposium was sponsored by the American Institute of Nutrition. Guest editor for this symposium was F. Bronner, De partment of BioStructure and Function, University of Connecticut Health Center, Farmington, CT. 2 To whom correspondence should be addressed: Dept. of Biostructure and Function, University Farmington, CT 06030.
0022-3166/92 $3.00 ©1992 American Institute of Nutrition. J. Nutr. 122: 641-643, 1992. 641
of Connecticut
Health Center,
Downloaded from https://academic.oup.com/jn/article-abstract/122/suppl_3/641/4755264 by East Carolina University user on 09 January 2019
FELIX BRONHER2
642
BRONNER TABLE 1 Regulatory effects of vitamin D on the steps of transcellular calcium transport
Step
Effect Enhances by 20-40% (1, 4, 5)
Binding to fixed organelles (Golgi, rough endoplasmic reticulum, mitochondria) Intracellular diffusion
Enhanced up to 100% (29)
Extrusion
Enhanced in direct proportion to cellular content of calbindin9K (1, 30) Ca-ATPase activity increased 200-300% (31, 32)
Paracellular calcium movement is necessarily down a chemical gradient for the reason given above. In the intestine the intercellular pathway consists of three sequential stretches: 1) the tight junction, 2) the in termediate junction and 3) a much wider basolateral space (21). It has been calculated (1) that the rate of calcium movement through the region of the tight junction is far slower than would be expected on the basis of simple diffusion. Hence the structure of the junction, with its compressed protein-lipid space, must hinder fluid and calcium movement appreciably. Hyperosmolar solutions, regardless of their chemical na ture, can cause the rate of passive calcium transport to double or triple (22). This presumably occurs be cause water moving into the hyperosmolar space causes the tissue to expand and the junctions to widen. This in turn must result from a modification of the cytoskeleton of the cell walls lining the junctions. Pappenheimer and colleagues (23-25) proposed that at least some amino acids cause contraction of the cy toskeleton of the cells lining the junction, thereby causing increased calcium flow. Many years ago, Wasserman and colleagues (26) reported that feeding Llysine caused calcium absorption to increase. It seems unlikely that amino acids or certain lipids act on the transcellular pathway. Action on the passive paracellular pathway, perhaps actin-mediated, seems a more logical explanation. Before concluding this overview, it is appropriate to discuss very briefly the regulation by vitamin D of active transcellular transport. As shown in Table 1, vitamin D acts on all aspects of transcellular calcium transport: it enhances entry, but only weakly (2040%); it increases calcium uptake by fixed organelles, extent uncertain; its presence leads to a doubling or tripling of the calcium pump activity, mechanism un known; and it increases overall calcium transport in direct proportion to the amount of calbindin-9K, the synthesis of which is directly and totally dependent on the amount of 1,25-dihydroxycholecalciferol, the active vitamin D metabolite, that reaches the cell. Thus
May involve a modulation of calcium channel open time (27), perhaps via an integral calcium-binding protein (28) Unknown Vitamin D-dependent
synthesis of calbindin
Unknown—modulation of conformational change of transmembrane elements of pump molecule leading to increased calcium propulsion through putative channel?
the major quantitative effect of vitamin D is to increase or modulate the amount of calbindin in the cell, the principal calcium ferry. It is therefore appropriate that the symposium includes a discussion of the regulation of the calbindin genes and their expression. Little is known about the modulation of the paracellular pathway and it is to be hoped this aspect will be subjected to more intensive study. Analysis of dis eases or defects that may affect calcium transport can contribute to defining possible modes of regulation and is therefore also included in the Symposium.
LITERATURE CITED 1. Bronner, F., Pansu, D. & Stein, W. D. (1986) An analysis of intestinal calcium transport across the rat intestine. Am. J. Physiol. 250: G561-G569. 2. Pansu, D., Bellaton, C., Roche, C. & Bronner, F. (1983) Duodenal and ileal calcium absorption in the rat and effects of vitamin D. Am. J. Physiol. 244: G695-G700. 3. Bronner, F. (1991) Calcium transport across epithelia. Int. Rev. Cytol. 131: 169-212. 4. Rasmussen, H., Fontaine, O., Max, E. E. & Goodman, D. P. (1979) The effect of l(alpha)-hydroxyvitamin D3 admin istration on calcium transport in chick intestine brush border membrane vesicles. J. Biol. Chem. 254: 2993-2999. 5. Miller, A., Ill & Bronner, F. (1981) Calcium uptake in isolated brush-border vesicles from rat small intestine. Biochem. J. 196: 391-401. 6. Schedi, H. P. &. Wilson, H. D. (1985) Calcium uptake by in testinal brush border membrane vesicles. Comparison with in vivo calcium transport. J. Clin. Invest. 76: 1871-1878. 7. Takito, J., Shinki, T., Sasaki, T. & Suda, T. (1990) Calcium uptake by brush-border and basolateral membrane vesicles in chick duodenum. Am. J. Physiol. 258: G16-G23. 8. Miller, A., Ill, Li, S. T. & Bronner, F. (1982) Characterization of calcium binding to brush border membranes from rat duo denum. Biochem. J. 208: 773-782. 9. Wilson, H. D., Schedi, H. P. &Christensen, K. (1989) Calcium uptake by brush-border membrane vesicles from the rat intes tine. Am. J. Physiol. 257: F446-F453. 10. Wasserman, R. H., Fullmer, C. S. & Taylor, A. N. (1978) The vitamin D-dependent calcium-binding proteins. In: Vitamin D. (Lawson, D. E. M., éd.), pp. 133-166, Academic Press, London, United Kingdom.
Downloaded from https://academic.oup.com/jn/article-abstract/122/suppl_3/641/4755264 by East Carolina University user on 09 January 2019
Entry
Mechanism
SYMPOSIUM: CURRENT CONCEPTS OF CALCIUM ABSORPTION
19. Tsukamoto, Y., Suki, W. N., Liang, C. T. & Sacktor, B. (1986) Caî+-dependentATPase in thébasolateral membranes of rat kidney cortex. J. Biol. Chem. 261: 2718-2724. 20. Kraus-Friedmann, N. (1990) Calcium sequestration in the liver. Cell Calcium 11: 625-640. 21. Trier, J. S. (1968) Morphology of the epithelium of the small intestine. In: Handbook of Physiology. Alimentary Canal. In testinal Absorption. (Code, C. F., ed.), vol. III. section 6, pp. 1125-1176, American Physiological Society, Washington, DC. 22. Pansu, D., Chapuy, M. C., Milani, M. & Bellaton, C. (1976) Transepithelial calcium transport enhanced by xylose
and glucose in the rat jejunal ligated loop. Calcif. Tissue Res. 21:45-52. 23. Pappenheimer, J. R. (1987) Physiological regulation of transepithelial impedance in the intestinal mucosa of rats and ham sters. J. Membr. Biol. 100: 137-148. 24. Pappenheimer, J. R. & Reiss, K. Z. (1987) Contribution of sol vent drag through intercellular junctions to absorption of nu trients by the small intestine of the rat. J. Membr. Biol. 100: 123-136. 25. Madara, J. L. & Pappenheimer, J. R. (1987) Structural basis for physiological regulation of paracellular pathways in intestinal epithelia. J. Membr. Biol. 100: 149-164. 26. Wasserman, R. H., Comar, C. L. &. Nold, M. M. (1956) The influence of amino acids and other organic compounds on the gastrointestinal absorption of calcium45 and strontium89 in the rat. J. Nutr. 59: 371-383. 27. Caff rey, J. M. & Farach-Carson, M. C. (1989) Vitamin D3 me tabolites modulate dihydropyridine-sensitive calcium currents in clonal rat osteosarcoma cells. J. Biol. Chem. 264: 2026520274. 28. Kowarski, S. & Schachter, D. (1980) Intestinal membrane cal cium-binding protein: Vitamin-D-dependent membrane com ponent of the intestinal calcium transport mechanism. J. Biol. Chem. 255: 10834-10840. 29. Weiser, M. M., Bloor, J. H., Dasmahapatra, A., Freedman, R. A. & MacLaughlin, J. A. (1981) Vitamin D-dependent rat intestinal Ca2+ transport. Ca2+ uptake by Golgi membranes and early nuclear events. In: Calcium and Phosphate Transport Across Biomembranes. (Bronner, F. & Peterlik, M., eds.), pp. 264-273, Academic Press, New York, NY. 30. Roche, C., Bellaton, C., Pansu, D., Miller, A., III & Bronner, F. (1986) Localization of vitamin D-dependent active Ca1+ transport in rat duodenum and relation to CaBP. Am. J. Physiol. 251:G314-G320. 31. Schiffl, H. & Binswager, U. (1980) Calcium ATPase and intes tinal calcium transport in uremie rats. Am. J. Physiol. 238: G424-G428. 32. Ghijsen, W. E. J. M. & van Os, C. H. (1982) l-alpha,25-dihydroxyvitamin D3 regulates ATP-dependent calcium transport in basolateral plasma membranes of rat enterocytes. Biochim. Bio phys. Acta 689: 170-172.
Downloaded from https://academic.oup.com/jn/article-abstract/122/suppl_3/641/4755264 by East Carolina University user on 09 January 2019
11. Nemere, I. (1990) OrgandÃ-es that bind calcium. In: Intracellular Calcium Regulation. (Bronner, F., ed.), pp. 163-179, WileyLiss, New York, NY. 12. Kretsinger, R. H., Mann, J. E. & Simmons, J. G. (1982) Model of the facilitated diffusion of calcium by the intestinal calcium binding protein. In: Vitamin D Chemical, Biochemical and Clinical Endocrinology of Calcium Metabolism. (Norman, A. W., Schaefer, K., Herrath, D. V. & Gringoleit, H.-G., eds.), pp. 233-246, DeGruyter, Berlin, Germany. 13. Feher, J. J. (1983) Facilitated calcium diffusion by intestinal calcium-binding protein. Am. J. Physiol. 244: C303-C307. 14. Feher, J. J. (1984) Measurement of facilitated calcium diffusion by a soluble calcium-binding protein. Biochim. Biophys. Acta 773: 91-98. 15. Feher, J. J. & Fullmer, C. S. (1988) Facilitated diffusion of cal cium by calcium-binding protein: Its role in intestinal calcium absorption. In: Cellular Calcium and Phosphate Transport in Health and Disease. (Bronner, F. & Peterlik, M., eds.), pp. 121126, Alan R. Liss, New York, NY. 16. Ghijsen, W. E. J. M., Dejong, M. D. & van Os, C. H. (1982) ATP-dependent calcium transport and its correlation with Ca2*-ATPase activity in basolateral plasma membranes of rat duodenum. Biochim. Biophys. Acta 689: 327-336. 17. Nellans, H. N. & Popovitch, J. R. (1984) Role of sodium in intestinal calcium transport. In: Epithelial Calcium and Phos phate Transport: Molecular and Cellular Aspects. (Bronner, F. &.Peterlik, M., eds.), pp. 301-306, Alan R. Liss, New York, NY. 18. Verma, A. K., Piloteo, A. G., Stanford, D. R., Wieben, E. D., Penniston, J. T., Strehler, E. E., Fischer, R., Heim, R., Vogel, G., Mathews, S., Strehler-Page, M.-A., James, P., Vorherr, T., Krebs, J. & Carafoli, E. (1988) Complete primary structure of a human plasma membrane Ca2+ pump. J. Biol. Chem. 263: 14152-14159.
643
Current Concepts of Calcium Absorption
Current Concepts of Calcium Absorption: An Overview Department of BioStructure and Function, University of Connecticut Health Center, Farmington, CT 06030 Transepithelial calcium transport in the intestine proceeds by two routes: a transcellular and a paracellular pathway (1). The transcellular route is dominant in the proximal intestine, largely the duodenum, whereas paracellular calcium movement takes place throughout the length of the intestine (2). Transcel lular movement involves three steps: I) entry across the brush border membrane of the enterocyte, 2) intracellular movement and 3) extrusion across the basolateral membrane. Directionality of the movement is assured by the cell structure, the brush border being located at the luminal cell surface, from which calcium enters the cell, whereas extrusion occurs at the basolateral membrane, i.e., the serosal pole of the cell. Moreover, because the extrusion capacity of the CaATPase, the pump enzyme, exceeds the rates of entry and intracellular diffusion, directionality is also as sured functionally. Entry into the cell is down an electrochemical gra dient and in all likelihood uses calcium channels (3). However, the existence of calcium channels in the brush border membrane of mucosal cells still awaits experimental proof. Calcium entry into the cell, as evaluated by uptake measurements that use right sideout brush border membrane vesicles, has been de scribed as the sum of a saturable and a nonsaturable step (4-7). The saturable step may represent the es tablished and significant binding of calcium to the in ner aspect of the brush border membrane vesicle (5, 8). It may also represent a carrier-mediated transport step (6, 9). However, if that were the case it would mean the enterocyte is equipped with two pump-leak systems, working in opposite directions. This is pos sible, but seems unlikely. Inside the cell, calcium must move through the cy toplasm. The rate of self-diffusion of calcium in an enterocyte such as the ileal cell has been calculated to be nearly two orders of magnitude too slow to allow calcium transfer to occur at the experimentally verified rate of transcellular movement (1). A cytosolic cal cium-binding protein, calbindin-9K, discovered some 25 years ago by Wasserman and colleagues (10), occurs
in duodenal cells at high enough concentrations (1) to assure a rate of intracellular flux sufficient to satisfy the established transcellular transport rate. Lysosomes and perhaps other mobile organelles may contribute to intracellular calcium movement (11). However, the quantitative considerations that have led to the pro posal that calbindin ferries calcium intracellularly (1, 12-15) must apply to all intracellular movement of calcium. Calcium extrusion is effected by the Ca-ATPase (16), with the Na+/Ca2+ exchanger probably contrib uting little to calcium transport (17). The capacity of this type of pump is some 25-30 nmol Ca-mg pro tein"1-min"1 (3). It should be emphasized, however, that the Ca-ATPase of the enterocyte has not yet been isolated or cloned. Hence, we do not know whether the cDNA coding a plasma membrane pump that has been isolated from a human teratoma library (18) is the same as that specifying the Ca-ATPase of the in testinal cell, nor whether the two Ca-ATPases are identical. Inasmuch as some Ca-ATPases are inhibited by vanadate, whereas this is not true for the kidney Ca-ATPase (19), and because the optimum pH of the liver Ca-ATPase differs from that of the plasma mem brane enzyme (20), all calcium pump molecules do not appear to be identical. Extrusion is against an electrochemical gradient. However, the overall transport, i.e., from intestinal lumen to the fluid bathing the serosal pole of the in testinal cell, is usually downhill, at least from a con centration viewpoint, inasmuch as the luminal calcium concentration is usually higher than the body fluid concentration of ~ 1 mmol Ca2+/L. 1Presented as part of a symposium: Current Concepts of Calcium Absorption, given at the 75th Annual Meeting of the Federation of American Societies for Experimental Biology, Atlanta, GA, April 22, 1991. The symposium was sponsored by the American Institute of Nutrition. Guest editor for this symposium was F. Bronner, De partment of BioStructure and Function, University of Connecticut Health Center, Farmington, CT. 2 To whom correspondence should be addressed: Dept. of Biostructure and Function, University Farmington, CT 06030.
0022-3166/92 $3.00 ©1992 American Institute of Nutrition. J. Nutr. 122: 641-643, 1992. 641
of Connecticut
Health Center,
Downloaded from https://academic.oup.com/jn/article-abstract/122/suppl_3/641/4755264 by East Carolina University user on 09 January 2019
FELIX BRONHER2
642
BRONNER TABLE 1 Regulatory effects of vitamin D on the steps of transcellular calcium transport
Step
Effect Enhances by 20-40% (1, 4, 5)
Binding to fixed organelles (Golgi, rough endoplasmic reticulum, mitochondria) Intracellular diffusion
Enhanced up to 100% (29)
Extrusion
Enhanced in direct proportion to cellular content of calbindin9K (1, 30) Ca-ATPase activity increased 200-300% (31, 32)
Paracellular calcium movement is necessarily down a chemical gradient for the reason given above. In the intestine the intercellular pathway consists of three sequential stretches: 1) the tight junction, 2) the in termediate junction and 3) a much wider basolateral space (21). It has been calculated (1) that the rate of calcium movement through the region of the tight junction is far slower than would be expected on the basis of simple diffusion. Hence the structure of the junction, with its compressed protein-lipid space, must hinder fluid and calcium movement appreciably. Hyperosmolar solutions, regardless of their chemical na ture, can cause the rate of passive calcium transport to double or triple (22). This presumably occurs be cause water moving into the hyperosmolar space causes the tissue to expand and the junctions to widen. This in turn must result from a modification of the cytoskeleton of the cell walls lining the junctions. Pappenheimer and colleagues (23-25) proposed that at least some amino acids cause contraction of the cy toskeleton of the cells lining the junction, thereby causing increased calcium flow. Many years ago, Wasserman and colleagues (26) reported that feeding Llysine caused calcium absorption to increase. It seems unlikely that amino acids or certain lipids act on the transcellular pathway. Action on the passive paracellular pathway, perhaps actin-mediated, seems a more logical explanation. Before concluding this overview, it is appropriate to discuss very briefly the regulation by vitamin D of active transcellular transport. As shown in Table 1, vitamin D acts on all aspects of transcellular calcium transport: it enhances entry, but only weakly (2040%); it increases calcium uptake by fixed organelles, extent uncertain; its presence leads to a doubling or tripling of the calcium pump activity, mechanism un known; and it increases overall calcium transport in direct proportion to the amount of calbindin-9K, the synthesis of which is directly and totally dependent on the amount of 1,25-dihydroxycholecalciferol, the active vitamin D metabolite, that reaches the cell. Thus
May involve a modulation of calcium channel open time (27), perhaps via an integral calcium-binding protein (28) Unknown Vitamin D-dependent
synthesis of calbindin
Unknown—modulation of conformational change of transmembrane elements of pump molecule leading to increased calcium propulsion through putative channel?
the major quantitative effect of vitamin D is to increase or modulate the amount of calbindin in the cell, the principal calcium ferry. It is therefore appropriate that the symposium includes a discussion of the regulation of the calbindin genes and their expression. Little is known about the modulation of the paracellular pathway and it is to be hoped this aspect will be subjected to more intensive study. Analysis of dis eases or defects that may affect calcium transport can contribute to defining possible modes of regulation and is therefore also included in the Symposium.
LITERATURE CITED 1. Bronner, F., Pansu, D. & Stein, W. D. (1986) An analysis of intestinal calcium transport across the rat intestine. Am. J. Physiol. 250: G561-G569. 2. Pansu, D., Bellaton, C., Roche, C. & Bronner, F. (1983) Duodenal and ileal calcium absorption in the rat and effects of vitamin D. Am. J. Physiol. 244: G695-G700. 3. Bronner, F. (1991) Calcium transport across epithelia. Int. Rev. Cytol. 131: 169-212. 4. Rasmussen, H., Fontaine, O., Max, E. E. & Goodman, D. P. (1979) The effect of l(alpha)-hydroxyvitamin D3 admin istration on calcium transport in chick intestine brush border membrane vesicles. J. Biol. Chem. 254: 2993-2999. 5. Miller, A., Ill & Bronner, F. (1981) Calcium uptake in isolated brush-border vesicles from rat small intestine. Biochem. J. 196: 391-401. 6. Schedi, H. P. &. Wilson, H. D. (1985) Calcium uptake by in testinal brush border membrane vesicles. Comparison with in vivo calcium transport. J. Clin. Invest. 76: 1871-1878. 7. Takito, J., Shinki, T., Sasaki, T. & Suda, T. (1990) Calcium uptake by brush-border and basolateral membrane vesicles in chick duodenum. Am. J. Physiol. 258: G16-G23. 8. Miller, A., Ill, Li, S. T. & Bronner, F. (1982) Characterization of calcium binding to brush border membranes from rat duo denum. Biochem. J. 208: 773-782. 9. Wilson, H. D., Schedi, H. P. &Christensen, K. (1989) Calcium uptake by brush-border membrane vesicles from the rat intes tine. Am. J. Physiol. 257: F446-F453. 10. Wasserman, R. H., Fullmer, C. S. & Taylor, A. N. (1978) The vitamin D-dependent calcium-binding proteins. In: Vitamin D. (Lawson, D. E. M., éd.), pp. 133-166, Academic Press, London, United Kingdom.
Downloaded from https://academic.oup.com/jn/article-abstract/122/suppl_3/641/4755264 by East Carolina University user on 09 January 2019
Entry
Mechanism
SYMPOSIUM: CURRENT CONCEPTS OF CALCIUM ABSORPTION
19. Tsukamoto, Y., Suki, W. N., Liang, C. T. & Sacktor, B. (1986) Caî+-dependentATPase in thébasolateral membranes of rat kidney cortex. J. Biol. Chem. 261: 2718-2724. 20. Kraus-Friedmann, N. (1990) Calcium sequestration in the liver. Cell Calcium 11: 625-640. 21. Trier, J. S. (1968) Morphology of the epithelium of the small intestine. In: Handbook of Physiology. Alimentary Canal. In testinal Absorption. (Code, C. F., ed.), vol. III. section 6, pp. 1125-1176, American Physiological Society, Washington, DC. 22. Pansu, D., Chapuy, M. C., Milani, M. & Bellaton, C. (1976) Transepithelial calcium transport enhanced by xylose
and glucose in the rat jejunal ligated loop. Calcif. Tissue Res. 21:45-52. 23. Pappenheimer, J. R. (1987) Physiological regulation of transepithelial impedance in the intestinal mucosa of rats and ham sters. J. Membr. Biol. 100: 137-148. 24. Pappenheimer, J. R. & Reiss, K. Z. (1987) Contribution of sol vent drag through intercellular junctions to absorption of nu trients by the small intestine of the rat. J. Membr. Biol. 100: 123-136. 25. Madara, J. L. & Pappenheimer, J. R. (1987) Structural basis for physiological regulation of paracellular pathways in intestinal epithelia. J. Membr. Biol. 100: 149-164. 26. Wasserman, R. H., Comar, C. L. &. Nold, M. M. (1956) The influence of amino acids and other organic compounds on the gastrointestinal absorption of calcium45 and strontium89 in the rat. J. Nutr. 59: 371-383. 27. Caff rey, J. M. & Farach-Carson, M. C. (1989) Vitamin D3 me tabolites modulate dihydropyridine-sensitive calcium currents in clonal rat osteosarcoma cells. J. Biol. Chem. 264: 2026520274. 28. Kowarski, S. & Schachter, D. (1980) Intestinal membrane cal cium-binding protein: Vitamin-D-dependent membrane com ponent of the intestinal calcium transport mechanism. J. Biol. Chem. 255: 10834-10840. 29. Weiser, M. M., Bloor, J. H., Dasmahapatra, A., Freedman, R. A. & MacLaughlin, J. A. (1981) Vitamin D-dependent rat intestinal Ca2+ transport. Ca2+ uptake by Golgi membranes and early nuclear events. In: Calcium and Phosphate Transport Across Biomembranes. (Bronner, F. & Peterlik, M., eds.), pp. 264-273, Academic Press, New York, NY. 30. Roche, C., Bellaton, C., Pansu, D., Miller, A., III & Bronner, F. (1986) Localization of vitamin D-dependent active Ca1+ transport in rat duodenum and relation to CaBP. Am. J. Physiol. 251:G314-G320. 31. Schiffl, H. & Binswager, U. (1980) Calcium ATPase and intes tinal calcium transport in uremie rats. Am. J. Physiol. 238: G424-G428. 32. Ghijsen, W. E. J. M. & van Os, C. H. (1982) l-alpha,25-dihydroxyvitamin D3 regulates ATP-dependent calcium transport in basolateral plasma membranes of rat enterocytes. Biochim. Bio phys. Acta 689: 170-172.
Downloaded from https://academic.oup.com/jn/article-abstract/122/suppl_3/641/4755264 by East Carolina University user on 09 January 2019
11. Nemere, I. (1990) OrgandÃ-es that bind calcium. In: Intracellular Calcium Regulation. (Bronner, F., ed.), pp. 163-179, WileyLiss, New York, NY. 12. Kretsinger, R. H., Mann, J. E. & Simmons, J. G. (1982) Model of the facilitated diffusion of calcium by the intestinal calcium binding protein. In: Vitamin D Chemical, Biochemical and Clinical Endocrinology of Calcium Metabolism. (Norman, A. W., Schaefer, K., Herrath, D. V. & Gringoleit, H.-G., eds.), pp. 233-246, DeGruyter, Berlin, Germany. 13. Feher, J. J. (1983) Facilitated calcium diffusion by intestinal calcium-binding protein. Am. J. Physiol. 244: C303-C307. 14. Feher, J. J. (1984) Measurement of facilitated calcium diffusion by a soluble calcium-binding protein. Biochim. Biophys. Acta 773: 91-98. 15. Feher, J. J. & Fullmer, C. S. (1988) Facilitated diffusion of cal cium by calcium-binding protein: Its role in intestinal calcium absorption. In: Cellular Calcium and Phosphate Transport in Health and Disease. (Bronner, F. & Peterlik, M., eds.), pp. 121126, Alan R. Liss, New York, NY. 16. Ghijsen, W. E. J. M., Dejong, M. D. & van Os, C. H. (1982) ATP-dependent calcium transport and its correlation with Ca2*-ATPase activity in basolateral plasma membranes of rat duodenum. Biochim. Biophys. Acta 689: 327-336. 17. Nellans, H. N. & Popovitch, J. R. (1984) Role of sodium in intestinal calcium transport. In: Epithelial Calcium and Phos phate Transport: Molecular and Cellular Aspects. (Bronner, F. &.Peterlik, M., eds.), pp. 301-306, Alan R. Liss, New York, NY. 18. Verma, A. K., Piloteo, A. G., Stanford, D. R., Wieben, E. D., Penniston, J. T., Strehler, E. E., Fischer, R., Heim, R., Vogel, G., Mathews, S., Strehler-Page, M.-A., James, P., Vorherr, T., Krebs, J. & Carafoli, E. (1988) Complete primary structure of a human plasma membrane Ca2+ pump. J. Biol. Chem. 263: 14152-14159.
643
